Email this article All about epidermodysplasia verruciformis (EV): An inherited skin disorder
Abstract
Epidermodysplasia verruciformis (EV) is an uncommon genetic skin condition characterized by a high vulnerability to specific types of human papillomavirus (HPV), increasing the likelihood of non-melanoma skin cancer. The disorder is inherited in an autosomal recessive pattern, and certain families exhibit mutations in the TMC6 or TMC8 genes situated on chromosome 17q25.3. During childhood, individuals with EV frequently develop flat-topped, papular lesions that resemble verrucae planae on their limbs, reddish-brown plaques, or lesions resembling pityriasis versicolor on their neck, trunk, and face. In addition, more than half of patients may experience actinic keratoses and cutaneous malignancies during their twenties or thirties. Diagnosis of EV involves a skin biopsy to examine histological characteristics and detect HPV presence in a skin lesion. Additionally, there is an acquired form of EV observed in individuals with weakened immune systems. Although no definitive treatments exist for EV, patients are advised to rigorously practice sun protection measures to reduce the risk of developing non-melanoma skin cancer. Regular skin examinations throughout a patient›s lifetime are also recommended to detect precancerous skin lesions and early-stage cancer.
Keywords
Full Text:
Full-text PDFReferences
Pfister H, editor Human papillomaviruses and skin cancer. Semin Cancer Biol; 1992.
Orth G. Human papillomaviruses associated with epidermodysplasia verruciformis in non-melanoma skin cancers: guilty or innocent? J Invest Dermatol. 2005;125(1):xii-xiii. DOI: 10.1111/j.0022-202X.2005.23811.x PMID: 15982294
Majewski S, Jablonska S. Why epidermodysplasia verruciformis - a rare genetic disease - has raised such great interest. Int J Dermatol. 2004;43(4):309-11. DOI: 10.1111/j.1365-4632.2004.01558.x PMID: 15090022
Alshammari R, Al-Issa A, Ghobara YA. Epidermodysplasia Verruciformis: A Rare Case Report. Cureus. 2020. DOI: 10.7759/cureus.9046
McLaughlin-Drubin ME. Human papillomaviruses and non-melanoma skin cancer. Semin Oncol. 2015;42(2):284-90. DOI: 10.1053/j.seminoncol.2014.12.032 PMID: 25843732
Horton JS, Stokes AJ. The transmembrane channel-like protein family and human papillomaviruses: Insights into epidermodysplasia verruciformis and progression to squamous cell carcinoma. Oncoimmunology. 2014;3(1):e28288. DOI: 10.4161/onci.28288 PMID: 24800179
Liu-Smith F, Jia J, Zheng Y. UV-Induced Molecular Signaling Differences in Melanoma and Non-melanoma Skin Cancer. Adv Exp Med Biol. 2017;996:27-40. DOI: 10.1007/978-3-319-56017-5_3 PMID: 29124688
de Jong SJ, Imahorn E, Itin P, Uitto J, Orth G, Jouanguy E, et al. Epidermodysplasia Verruciformis: Inborn Errors of Immunity to Human Beta-Papillomaviruses. Front Microbiol. 2018;9:1222. DOI: 10.3389/fmicb.2018.01222 PMID: 29946305
Ramoz N, Rueda LA, Bouadjar B, Montoya LS, Orth G, Favre M. Mutations in two adjacent novel genes are associated with epidermodysplasia verruciformis. Nat Genet. 2002;32(4):579-81. DOI: 10.1038/ng1044 PMID: 12426567
Orth G. Genetics of epidermodysplasia verruciformis: Insights into host defense against papillomaviruses. Semin Immunol. 2006;18(6):362-74. DOI: 10.1016/j.smim.2006.07.008 PMID: 17011789
Foong HB, Ibrahimi OA, Elpern DJ, Tyring S, Rady P, Carlson JA. Multiple facial seborrheic keratosis-like lesions in a young woman with epidermodysplasia verruciformis. Int J Dermatol. 2008;47(5):476-8. DOI: 10.1111/j.1365-4632.2008.03559.x PMID: 18412865
Sa NB, Guerini MB, Barbato MT, Di Giunta G, Nunes DH. Epidermodysplasia verruciformis: clinical presentation with varied forms of lesions. An Bras Dermatol. 2011;86(4 Suppl 1):S57-60. DOI: 10.1590/s0365-05962011000700014 PMID: 22068772
Androphy EJ, Dvoretzky I, Lowy DR. X-linked inheritance of epidermodysplasia verruciformis. Genetic and virologic studies of a kindred. Arch Dermatol. 1985;121(7):864-8. PMID: 2990354
McDermott DF, Gammon B, Snijders PJ, Mbata I, Phifer B, Howland Hartley A, et al. Autosomal dominant epidermodysplasia verruciformis lacking a known EVER1 or EVER2 mutation. Pediatr Dermatol. 2009;26(3):306-10. DOI: 10.1111/j.1525-1470.2008.00853.x PMID: 19706093
Li SL, Duo LN, Wang HJ, Dai W, Zhou EH, Xu YN, et al. Identification of LCK mutation in a family with atypical epidermodysplasia verruciformis with T-cell defects and virus-induced squamous cell carcinoma. Br J Dermatol. 2016;175(6):1204-9. DOI: 10.1111/bjd.14679 PMID: 27087313
de Jong SJ, Crequer A, Matos I, Hum D, Gunasekharan V, Lorenzo L, et al. The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to beta-papillomaviruses. J Exp Med. 2018;215(9):2289-310. DOI: 10.1084/jem.20170308 PMID: 30068544
Przybyszewska J, Zlotogorski A, Ramot Y. Re-evaluation of epidermodysplasia verruciformis: Reconciling more than 90 years of debate. J Am Acad Dermatol. 2017;76(6):1161-75. DOI: 10.1016/j.jaad.2016.12.035 PMID: 28196644
Meyers JM, Grace M, Uberoi A, Lambert PF, Munger K. Inhibition of TGF-beta and NOTCH Signaling by Cutaneous Papillomaviruses. Front Microbiol. 2018;9:389. DOI: 10.3389/fmicb.2018.00389 PMID: 29568286
Olczak P, Wong M, Tsai HL, Wang H, Kirnbauer R, Griffith AJ, et al. Vaccination with human alphapapillomavirus-derived L2 multimer protects against human betapapillomavirus challenge, including in epidermodysplasia verruciformis model mice. Virology. 2022;575:63-73. DOI: 10.1016/j.virol.2022.08.006 PMID: 36070626
Ghittoni R, Accardi R, Hasan U, Gheit T, Sylla B, Tommasino M. The biological properties of E6 and E7 oncoproteins from human papillomaviruses. Virus Genes. 2010;40(1):1-13. DOI: 10.1007/s11262-009-0412-8 PMID: 19838783
Akgul B, Lemme W, Garcia-Escudero R, Storey A, Pfister HJ. UV-B irradiation stimulates the promoter activity of the high-risk, cutaneous human papillomavirus 5 and 8 in primary keratinocytes. Arch Virol. 2005;150(1):145-51. DOI: 10.1007/s00705-004-0398-4 PMID: 15654507
Cubie HA. Diseases associated with human papillomavirus infection. Virology. 2013;445(1-2):21-34. DOI: 10.1016/j.virol.2013.06.007 PMID: 23932731
Pfister H. [Biology of epidermodysplasia verruciformis-associated HPV]. Hautarzt. 2011;62(1):17-21. DOI: 10.1007/s00105-010-2030-8 PMID: 21113568
Patel T, Morrison LK, Rady P, Tyring S. Epidermodysplasia verruciformis and susceptibility to HPV. Dis Markers. 2010;29(3-4):199-206. DOI: 10.3233/DMA-2010-0733 PMID: 21178278
Mertz KD, Schmid M, Burger B, Itin P, Palmedo G, Scharer L, et al. Detection of Merkel cell polyomavirus in epidermodysplasia-verruciformis-associated skin neoplasms. Dermatology. 2011;222(1):87-92. DOI: 10.1159/000321880 PMID: 21099200
Kwon EK, Halvorson CR, Rady P, Tyring S, Nguyen HP, Kao GF, et al. Merkel cell polyomavirus detection in a patient with familial epidermodysplasia verruciformis. Pediatr Dermatol. 2013;30(4):505-7. DOI: 10.1111/pde.12130 PMID: 23535066
Michael KM, Waterboer T, Pfister H, Gariglio M, Majewski S, Favre M, et al. Seroreactivity of 38 human papillomavirus types in epidermodysplasia verruciformis patients, relatives, and controls. J Invest Dermatol. 2010;130(3):841-8. DOI: 10.1038/jid.2009.356 PMID: 19924140
Saeidian AH, Youssefian L, Naji M, Mahmoudi H, Barnada SM, Huang C, et al. Whole transcriptome-based skin virome profiling in typical epidermodysplasia verruciformis reveals alpha-, beta-, and gamma-HPV infections. JCI Insight. 2023;8(5). DOI: 10.1172/jci.insight.162558 PMID: 36602881
Bostan E, Akdogan N, Gokoz O. Epidermodysplasia Verruciformis After Hematopoietic Stem Cell Transplantation in a Patient With Severe Combined Immunodeficiency Syndrome. Am J Dermatopathol. 2021;43(5):e65-e7. DOI: 10.1097/DAD.0000000000001918 PMID: 33577180
Moore S, Rady P, Tyring S. Acquired epidermodysplasia verruciformis: clinical presentation and treatment update. Int J Dermatol. 2022;61(11):1325-35. DOI: 10.1111/ijd.15857 PMID: 34403500
Limmer AL, Wu JH, Doan HQ, Rady PL, Tyring SK. Acquired epidermodysplasia verruciformis: a 10-year anniversary update. Br J Dermatol. 2020;182(3):790-2. DOI: 10.1111/bjd.18549 PMID: 31545504
Kamili QUA, Seeborg FO, Saxena K, Nicholas SK, Banerjee PP, Angelo LS, et al. Severe cutaneous human papillomavirus infection associated with natural killer cell deficiency following stem cell transplantation for severe combined immunodeficiency. J Allergy Clin Immunol. 2014;134(6):1451-3 e1. DOI: 10.1016/j.jaci.2014.07.009 PMID: 25159470
Abd Hamid IJ, Slatter MA, McKendrick F, Pearce MS, Gennery AR. Long-term outcome of hematopoietic stem cell transplantation for IL2RG/JAK3 SCID: a cohort report. Blood. 2017;129(15):2198-201. DOI: 10.1182/blood-2016-11-748616 PMID: 28209722
Burger B, Kind F, Spoerri I, Rutten A, Battegay M, Hausermann P, et al. HIV-positive child with epidermodysplasia verruciformis-like lesions and homozygous mutation in TMC6. AIDS. 2010;24(17):2758-60. DOI: 10.1097/QAD.0b013e32833fdfca PMID: 20980872
Burger B, Sporri I, Stegmann DA, De Mesmaker J, Schaub S, Itin PH, et al. Risk of Cutaneous Squamous Cell Carcinoma Development in Renal Transplant Recipients Is Independent of TMC/EVER Alterations. Dermatology. 2015;231(3):245-52. DOI: 10.1159/000435910 PMID: 26227733
Carre D, Dompmartin A, Verdon R, Comoz F, Le Brun E, Freymuth F, et al. Epidermodysplasia verruciformis in a patient with HIV infection: no response to highly active antiretroviral therapy. Int J Dermatol. 2003;42(4):296-300. DOI: 10.1046/j.1365-4362.2003.01707_2.x PMID: 12694498
Rallis E, Paparizos V, Kyriakis K, Katsambas A. Treatment of epidermodysplasia verruciformis in human immunodeficiency virus-positive patients. J Eur Acad Dermatol Venereol. 2009;23(2):195-6. DOI: 10.1111/j.1468-3083.2008.02769.x PMID: 18462300
da Cruz Silva LL, de Oliveira WRP, Sotto MN. Epidermodysplasia verruciformis: revision of a model of carcinogenic disease. Surg Exp Pathol. 2019;2(1):20. DOI: 10.1186/s42047-019-0046-7
Araujo MG, Magalhaes GM, Garcia LC, Vieira EC, Carvalho-Leite MLR, Guedes ACM. Update on human papillomavirus - Part II: complementary diagnosis, treatment and prophylaxis. An Bras Dermatol. 2021;96(2):125-38. DOI: 10.1016/j.abd.2020.11.005 PMID: 33637397
Barcelos AC, Sotto MN. Comparative analysis of the expression of cytokeratins (1, 10, 14, 16, 4), involucrin, filaggrin and e-cadherin in plane warts and epidermodysplasia verruciformis plane wart-type lesions. J Cutan Pathol. 2009;36(6):647-54. DOI: 10.1111/j.1600-0560.2008.01127.x PMID: 19515043
Westphal K, Akgül B, Storey A, Nindl I. Cutaneous Human Papillomavirus E7 Type-Specific Effects on Differentiation and Proliferation of Organotypic Skin Cultures. Anal Cell Pathol. 2009;31(3):213-26. DOI: 10.1155/2009/584185
Anadolu R, Oskay T, Erdem C, Boyvat A, Terzi E, Gurgey E. Treatment of epidermodysplasia verruciformis with a combination of acitretin and interferon alfa-2a. J Am Acad Dermatol. 2001;45(2):296-9. DOI: 10.1067/mjd.2001.114575 PMID: 11464195
Janssen K, Lucker GP, Houwing RH, van Rijssel R. Epidermodysplasia verruciformis: unsuccessful therapeutic approach with imiquimod. Int J Dermatol. 2007;46 Suppl 3:45-7. DOI: 10.1111/j.1365-4632.2007.03513.x PMID: 17973891
Berthelot C, Dickerson MC, Rady P, He Q, Niroomand F, Tyring SK, et al. Treatment of a patient with epidermodysplasia verruciformis carrying a novel EVER2 mutation with imiquimod. J Am Acad Dermatol. 2007;56(5):882-6. DOI: 10.1016/j.jaad.2007.01.036 PMID: 17368633
Karrer S, Szeimies RM, Abels C, Wlotzke U, Stolz W, Landthaler M. Epidermodysplasia verruciformis treated using topical 5-aminolaevulinic acid photodynamic therapy. Br J Dermatol. 1999;140(5):935-8. DOI: 10.1046/j.1365-2133.1999.02830.x PMID: 10354037
de Oliveira WR, Neto CF, Rivitti EA. The lack of a clinical effect of cimetidine in the treatment of epidermodysplasia verruciformis. J Am Acad Dermatol. 2004;50(6):e14; author reply e5. DOI: 10.1016/j.jaad.2003.12.037 PMID: 15153919
Micali G, Nasca MR, Dall'Oglio F, Musumeci ML. Cimetidine therapy for epidermodysplasia verruciformis. J Am Acad Dermatol. 2003;48(2 Suppl):S9-10. DOI: 10.1067/mjd.2003.111 PMID: 12582373
de Oliveira WR, da Cruz Silva LL, Neto CF, Tyring S. Deleterious Effect of Radiation Therapy on Epidermodysplasia Verruciformis Patients. J Cutan Med Surg. 2015;19(4):416-21. DOI: 10.1177/1203475415576859 PMID: 26156649
Rajabi MT, Ghasemi H, Safizadeh M, Jamshidi S, Asadi-Amoli F, Abrishami Y, et al. Conjunctival squamous cell carcinoma with intraocular invasion after radiotherapy in epidermodysplasia verruciformis. Can J Ophthalmol. 2014;49(2):e43-6. DOI: 10.1016/j.jcjo.2013.12.009 PMID: 24767238
Burger B, Itin PH. Epidermodysplasia verruciformis. Curr Probl Dermatol. 2014;45:123-31. DOI: 10.1159/000356068 PMID: 24643182
Refbacks
- There are currently no refbacks.
Copyright (c) 2024 © The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.